ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma
In lymphoma refractory to chemotherapy, where expected survival was around six months, a single CAR-T infusion produced responses in 82% of patients and long-term remission in about 40%.
ZUMA-1 was a multicentre single-arm phase 2 trial of axicabtagene ciloleucel (axi-cel), a CD19 CAR-T with a CD28 costimulatory domain, in 111 enrolled and 101 treated patients with refractory diffuse large B-cell, primary mediastinal or transformed follicular lymphoma. Manufacturing succeeded in 99% and the median time from apheresis to delivery was 17 days. The objective response rate was 82% with complete response in 54%; at a median follow-up of 15.4 months 42% remained in response (40% in complete response), and 18-month overall survival was 52%. Grade 3 or higher cytokine release syndrome occurred in 13% and neurological events in 28%. Five-year follow-up showed overall survival of about 43% with a plateau, consistent with cure in a substantial minority. It supported FDA approval in October 2017.
- 111 enrolled, 101 treated patients with chemotherapy-refractory large B-cell lymphoma; 22 centres.
- Manufacturing success 99%; median 17 days from apheresis to delivery; no bridging chemotherapy allowed.
- Objective response 82%; complete response 54%; 42% still responding at 15.4 months median follow-up.
- 18-month overall survival 52%; 5-year overall survival about 43% with a plateau.
- Grade 3 or higher CRS 13%; grade 3 or higher neurological events 28%; 3 deaths during treatment.
ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.
- Single-arm with a historical comparator (SCHOLAR-1).
- No bridging therapy was allowed, selecting patients with slower-growing disease.
- Roughly 60% of patients eventually relapsed or died; long-term survivors are a minority.
- Toxicity required intensive-care-capable centres; real-world use has since expanded with prophylactic steroids.
ZUMA-2 gave patients with BTK-inhibitor-refractory mantle cell lymphoma, who previously had a median survival under a year, a therapy with durable remissions in a substantial fraction. Brexu-cel is now standard after BTK inhibitor failure and CAR-T is being tested earlier in the disease. Neurotoxicity rates are higher than in other lymphoma CAR-T trials.
JULIET, with ZUMA-1, showed that CAR-T could rescue a substantial minority of adults with chemotherapy-refractory lymphoma and that complete responders often stay in remission. The lower toxicity of a 4-1BB construct and the option of bridging therapy made it usable in a broader population. The high drop-out between enrolment and infusion remains a lesson about turnaround time.
Pages like this
not linked directly; found by shared links- ProductBrexucabtagene autoleucel
Shares ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors, Gilead Sciences (incl. Kite), ICANS (neurotoxicity), Cytokine release syndrome (CRS).
- Key paperTRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma
Shares ZUMA-7, ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early, ICANS (neurotoxicity), Cytokine release syndrome (CRS).
- ProductTisagenlecleucel
Shares JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma, ICANS (neurotoxicity), Follicular lymphoma, Cytokine release syndrome (CRS).
- ProductLisocabtagene maraleucel
Shares ICANS (neurotoxicity), Follicular lymphoma, Cytokine release syndrome (CRS), CD19.
- TrialBELINDA
Shares JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma, ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early, Diffuse large B-cell lymphoma, CAR-T cell therapy.
- Key paperCARTITUDE-1: cilta-cel, a BCMA CAR-T, in heavily pretreated myeloma
Shares ICANS (neurotoxicity), Objective response rate (ORR), Cytokine release syndrome (CRS), Manufacturing cost and time for living and radioactive medicines.
- PairingEarly relapse: CAR-T before transplant
Shares ZUMA-7, ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early, Diffuse large B-cell lymphoma, CAR-T cell therapy.
- IdeaHead-to-head bispecific vs CAR-T in second-line LBCL
Shares Axicabtagene ciloleucel, Manufacturing cost and time for living and radioactive medicines, Diffuse large B-cell lymphoma, CAR-T cell therapy.